Lecture 13

Question 1

what is the pathology of parkinsons disease?

Answer 1

degeneration of dopamine neurons in the substantia nigra (and other areas; olfactory)

Question 2

what is parkinsons disease?

Answer 2

• highly prevalent neurodegenerative disorder

- characterised by motor dysfunction and non motor symptoms

Question 3

where is the highest incidence of parkinsons disease seen and the mean age of onset?

Answer 3

• seen most in older people

- age of onset = 57

Question 4

parkinsons involves death of nigrastriatal neurons of the basal ganglia, what is the function of the cells in a non-affected basal ganglia?

Answer 4

• cells of the SN produce+ release dopamine
• dopamine affects other centres
• main centres affected = dorsal striatum
• dorsal striatum involved in motor function

Question 5

2 functions of dopamine

Answer 5

1) transmits signals between the areas in the brain that when working normally coordinate smooth and balanced muscle movement
2) control functions related to mood

Question 6

what are dopamine precursors and antagonists?

Answer 6

precursors = medication the brain converts to dopamine
antagonists = directly stimulate nerves in the brain that are not naturally being stimulated by dopamine
- have been prescribed to patients and shown some effect

Question 7

why is the basic circuit in the basal ganglia important?

Answer 7

• if you remove parts of the circuit it will mess it up

- causes sustained inhibition to the thalamus

Question 8

what does wrong in parkinsons?

Answer 8

cells of substantia nigra degenerate - no longer producing adequate amounts of dopamine - neurons of striatum are no longer well regulated and do not behave normally - resulting in symptoms of parkinsons

Question 9

what are motor symptoms of parkinsons?

Answer 9

1) slow movement
2) tremors
3) muscle rigidity
4) postural change
5) decreased spontaneous movements e.g. blinking
6) gait disorders - slow steps

Question 10

what are non - motor symptoms of parkinsons?

Answer 10

1) depression
2) bowel problems
3) increased sweating
4) weight loss
5) excess salivation and repsiratory problems

Question 11

what is a lewy body and effects?

Answer 11

• parts of the brain affected by parkinsons
• as the disease progresses the lewy bodies spread - as more of the cortex is affected the affects of the diseases are more severe

Question 12

describe treatment of parkinsons with levodopa (L-DOPA)?

Answer 12

• converted by neurons to dopamine
• can cross blood-brain barrier (dopamine cannot)
• L-DOPA can be matabolised therefore prescribed with carbidopa which inhibits dopamine metabolism
• can produce dyskinesias (uncontrolled movements) and other side effects

Question 13

describe treatment with dopamine agonists?

Answer 13

• not metabolised into dopamine but act like dopamine
• used with L-DOPA in young patients
• similar side effects to L-DOPA but less involuntary movements - cause hallucinations

Question 14

what can be give to stop dopamine degradation?

Answer 14

inhibitors

Question 15

what is thalamotomy surgery?

Answer 15

• destruction of small parts of the thalamus which relays messages/sensations
• can caused slurred speech / coordination problems

Question 16

what is pallidotomy srugery?

Answer 16

• destruction of small parts of the globus pallidus

- interrupts pathways between globus pallidus and thalamus

Question 17

what is deep brain stimulation and an advantage?

Answer 17

• pacemaker like units
• stimulate parts of the brain to calm down tremors
  advantage over surgery it is reversible(can be switched off)

Question 18

describe human foetal cell transplantation

Answer 18

• 6-9 week old human foetuses contain dopamanergic neurons
• these neurons can survive, re-inervate the striatum
• difficult operation and unethical
• increase in dopa uptake seen
• some patients had improvement 18 years post-grafting
• proof of principle that cell transplantation works

Question 19

where else can you find dopamine producing cells?

Answer 19

pigmented retinal epithelium

Question 20

what are 2 factors which treatment of parkinsons by PSCs depends on?

Answer 20

1) you can differentiate the PSCs to the correct cell type, ideally efficiently
2) the cell type you make needs to be physiologically mature

Question 21

how would you manufacture pluripotent stem cells?

Answer 21

either derived from blastocyst or induced pluripotent stem cells

Question 22

once you have worked out the factors needed to get the correct cells differentiated and you have the neural epithelium what has the happen?

Answer 22

• have to go through the correct neurogenesis

- create cultures of specific part of midbrain where dopaminergic neurons form

Question 23

2 things which need to be done to make dopaminergic neurons from pluripotent stem cells?

Answer 23

1) supress meso/endoderm differentiation - promote ectoderm

2) inhibit BMP and TGFbeta signalling